Modulation of cAMP microdomains to treat heart failure


Funding ID

81Z2710108

Project number

485

Institution
Universitätsklinikum Hamburg-Eppendorf
Project leader
Viacheslav Nikolaev
Site
Hamburg/Kiel/Lübeck
Short description

The ubiquitous second messenger cAMP plays central roles in the regulation of cardiac function and diseases such as hypertrophy and heart failure. Especially the stimulation of … 

The ubiquitous second messenger cAMP plays central roles in the regulation of cardiac function and diseases such as hypertrophy and heart failure. Especially the stimulation of cardiomyocyte ?-adrenoceptors leads to strong contractile response and disease progression, while other membrane receptors coupled to the stimulatory G-protein (Gs) play less prominent role. Beta-blockers are therefore central to the therapy but lead to non-cardiac side-effects which limit patient compliance. This project will test the hypothesis that cardiomyocyte-specific delivery of a dominant negative Gs mutant should provide beneficial antihypertrophic effect without systemic side-effects. This mutant will be studied in mouse diseased models and introduced into AAV for gene therapy studies.

Project type
Partner Site Projects
Keywords
cAMP, microdomains, hypertrophy, beta-blocker, AAV, genetherapy
Topic
cardiac hypertrophy/remodeling
Funding
€ 491.801,84
Begin
29.10.2014
End
31.12.2018